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This article investigates how development education campaigns affect schoolchildren's understanding of both global and domestic poverty, through examining the 2012 Lenten campaign by the Irish agency, Trócaire. It analyses Trócaire campaign material as well as its reception by schoolchildren, aged 10-12. We found the material contained neo-colonial stereotypes about Africa as a primitive place dependent on Western aid, displaying continuity with the prior 'Black Baby Phenomenon'. This refers to the collection boxes Irish children were given with a picture of a black baby on them, which fostered an understanding of Africans as helpless childlike victims, Children in our focus groups understood the Africans portrayed by the Trócaire campaign as hopeless, primitive, intellectually inferior Others. Furthermore, this there was strong indication that this imagery fostered social distance towards ethnic minorities in Ireland and encouraged children to minimise domestic poverty, through considering this to be only an issue in 'developing countries'.

The use of actographs for studying animal activity is discussed. Described are running recorders for rodents, perching and feeding recorders for birds, and tilting box recorders for studying the movement of reptiles, amphibians, and arthropods. (CW)

Context: Many medical schools have a distributed model for clinical clerkship education, challenging our ability to determine student gaps during clinical education. With the graduating class of 2017, A.T. Still University's School of Osteopathic Medicine in Arizona (ATSU-SOMA) began requiring additional online curricula for all clerkship courses., Objectives: To determine whether third year and fourth year students receiving ATSU-SOMA's online curricula during core clerkships performed better overall on national standardized examinations than students from previous years who had not received the curricula, and whether scores from online coursework correlated with outcomes on standardized examinations as possible early predictors of success., Methods: This retrospective cohort study analyzed existing data (demographics and assessments) from ATSU-SOMA classes of 2017-2020 (curriculum group) and 2014-2016 (precurriculum group). The effect of the curriculum on national standardized examinations (Comprehensive Osteopathic Medical Achievement Test [COMAT] and Comprehensive Osteopathic Medical Licensing Examination of the United States [COMLEX-USA]) was estimated using augmented inverse probability weighting (AIPW). Correlations between assignment scores and national standardized examinations were estimated using linear regression models., Results: The curriculum group had 405 students with a mean (standard deviation [SD]) age of 25.7 (±3.1) years. Two hundred and fifteen (53.1%) students in the curriculum group were female and 190 (46.9%) were male. The precurriculum group had 308 students (mean ± SD age, 26.4 ± 4.2 years; 157 [51.0%] male; 151 [49.0%] female). The online curriculum group had higher COMAT clinical subject exam scores in obstetrics and gynecology, osteopathic principles and practice (OPP), psychiatry, and surgery (all p≤0.04), as well as higher COMLEX-USA Level 2-Cognitive Evaluation (CE) family medicine and OPP subscores (both p≤0.03). The curriculum group had a 9.4 point increase in mean total COMLEX-USA Level 2-CE score (p=0.08). No effect was found for the curriculum overall on COMAT mean or COMLEX-USA Level 2-Performance Evaluation scores (all p≥0.11). Total coursework scores in each core clerkship, excluding pediatrics, were correlated with COMAT mean score (all adjusted p≤0.03). Mean scores for five of the seven assignment types in core clerkships, excluding evidence based medicine types, were positively correlated with COMAT mean scores (all adjusted p≤0.049). All assignment types correlated with COMLEX-USA Level 2-CE total score (all adjusted p≤0.04), except interprofessional education (IPE)., Conclusions: Results from this study of 713 students from ATSU-SOMA suggested that our online curriculum supplemented clinic based learning during clerkship courses and improved student outcomes on national standardized examinations., (© 2021 Kelli Glaser et al., published by De Gruyter, Berlin/Boston.)

When the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a global health emergency, Colleges of Osteopathic Medicine (COMs) debated the role of medical students during this developing pandemic. Initially, the discussion included whether medical students were essential personnel contributing to meaningful patient care. Many questions arose regarding how COVID-19 would affect medical education and if the changes would be temporary or continue for a significant period of time. Due to the lack of availability of personal protective equipment (PPE) and a decreased focus on clinical education within many healthcare settings, in March the American Association of Colleges of Osteopathic Medicine (AACOM) declared that medical students were not essential personnel and recommended that COMs take a 'pause' and remove students from the clinical environment. This 'pause' would allow COMs time to assess where medical education could continue, to define the critical pieces of clinical education that required a clinical environment and to address how medical students could contribute during the pandemic. The AACOM Clinical Educators group began to meet on a weekly basis during this time so that Clinical Deans from Osteopathic medical schools across the country could collaborate, share ideas, discuss current challenges, and co-create a system to deliver medical education realizing the limitations of in-person clinical training., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Heiles et al.)

Inhibition of ataxia-telangiectasia mutated (ATM) during radiotherapy of glioblastoma multiforme (GBM) may improve tumor control by short-circuiting the response to radiation-induced DNA damage. A major impediment for clinical implementation is that current inhibitors have limited central nervous system (CNS) bioavailability; thus, the goal was to identify ATM inhibitors (ATMi) with improved CNS penetration. Drug screens and refinement of lead compounds identified AZ31 and AZ32. The compounds were then tested in vivo for efficacy and impact on tumor and healthy brain. Both AZ31 and AZ32 blocked the DNA damage response and radiosensitized GBM cells in vitro AZ32, with enhanced blood-brain barrier (BBB) penetration, was highly efficient in vivo as radiosensitizer in syngeneic and human, orthotopic mouse glioma model compared with AZ31. Furthermore, human glioma cell lines expressing mutant p53 or having checkpoint-defective mutations were particularly sensitive to ATMi radiosensitization. The mechanism for this p53 effect involves a propensity to undergo mitotic catastrophe relative to cells with wild-type p53. In vivo , apoptosis was >6-fold higher in tumor relative to healthy brain after exposure to AZ32 and low-dose radiation. AZ32 is the first ATMi with oral bioavailability shown to radiosensitize glioma and improve survival in orthotopic mouse models. These findings support the development of a clinical-grade, BBB-penetrating ATMi for the treatment of GBM. Importantly, because many GBMs have defective p53 signaling, the use of an ATMi concurrent with standard radiotherapy is expected to be cancer-specific, increase the therapeutic ratio, and maintain full therapeutic effect at lower radiation doses. Mol Cancer Ther; 17(8); 1637-47. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Significant loss of RNA followed by severely reduced cellular protein pool, a phenomenon termed host shutoff, is associated with a number of lytic virus infections and is a critical player in viral pathogenesis. Until recently, viral DNA exonucleases were associated only with processing of viral genomic DNA and its encapsidation. However, recent observations have identified host shutoff and exonuclease function for the highly conserved viral exonucleases in γ-herpesviruses, which include Kaposi's sarcoma-associated herpesvirus, Epstein-Barr virus and the mouse model murine gammaherpesvirus-68, also referred to as MHV-68. In this study, we show that although ablation of the MHV-68 exonuclease ORF37 caused a restrictive phenotype in WT IFN-α/β receptor-positive cells such as NIH 3T3, lack of ORF37 was tolerated in cells lacking the IFN-α/β receptor: the ORF37Stop virus was capable of forming infectious particles and caused loss of mRNA in IFN-α/β receptor knockout cells. Moreover, ORF37Stop virus was able to establish lytic infection in the lungs of mice lacking the IFN-α/β receptor. These observations provide evidence that lytic MHV-68 infection and subsequent loss of mRNA can take place independently of ORF37. Moreover, efficient growth of ORF37Stop virus also identifies a role for this family of viral nucleases in providing a window of opportunity for virus growth by overcoming type I IFN-dependent responses.

Epidemiologic studies in women with recurrent Candida vaginitis have been hampered in the past by the lack of a reproducible typing system. Several molecular probes have now been developed that have the ability to differentiate strains of Candida albicans and give reproducible results. In this investigation, 24 women with Candida vaginitis were studied in a longitudinal fashion for 30 days following short-course antifungal therapy. Seven women with either recurrent vaginitis or with multiple culture-positive sites with C. albicans were included in an epidemiological study. A total of 18 isolates of C. albicans (12 vaginal and six rectal) were typed utilizing restriction fragment length polymorphisms of rDNA. This technique was able to differentiate five different strains of C. albicans. Our epidemiologic study revealed that vaginal and rectal strains recovered from the same women were usually different. None of our patients had a similar vaginal and rectal strain prior to treatment, and only one patient had the same strain isolated from both the rectum and the vagina at the time of recurrence. On the other hand, we found that the same strain of C. albicans was initially and later recovered from the vagina in four of five women who failed treatment or developed recurrent vaginitis. These results suggest that recurrent episodes of C. albicans vaginitis, following short-course antifungal therapy, are often due to relapse of the original infecting strain and not due to autoinoculation from the rectum.(ABSTRACT TRUNCATED AT 250 WORDS)

Following EMS mutagenesis, three estramustine (EM) resistant DU 145 human prostatic carcinoma cell lines were clonally selected by exposure to incrementally increasing concentrations of the drug. Although only low levels of resistance (approximately 3-fold) were attainable, this resistance was stable in the absence of continuous drug exposure. These EM-resistant clones (EMR 4,9,12) did not exhibit cross resistance to vinblastine, taxol, or adriamycin, and had collateral sensitivity to cytochalasin B. None of the lines had elevated expression of P-glycoprotein mRNA or glutathione S-transferase activity, suggesting a phenotype distinct from the classic multi-drug resistance phenotype. This conclusion was supported further by the observation that two MDR cell lines (FLC mouse erythroleukaemic and SKOV3 human ovarian carcinoma cells) showed sensitivity to EM. Fluorescent activated cell sorting analysis of the effects of EM on cell cycle traverse revealed that at EM concentrations up to 20 microM an increasing percentage of wild type cells were blocked in G2/M; no such effect occurred in EMR lines. Differential interference contrast microscopy was employed to study EM's effect on mitosis. EMR lines were able to form functional, albeit smaller, spindles at EM concentrations that resulted in chromosomal disorganisation and inhibition of mitotic progression in wild type cells. EMR lines were able to progress through mitosis and cytokinesis at the same rate as untreated cells. Tritiated EM was used to evaluate potential drug uptake/efflux mutations in ERM clones. EMR 4 and 9 incorporate less EM than wild type cells; however, they have significantly decreased cellular volumes. The initial efflux rate constants for EMR clones were greater than for wild type cells. Within 5 min greater than 70% of the drug was lost from resistant cells compared to a 50% loss by the wild type. Although the specific mechanisms of resistance have yet to be defined, the lack of collateral resistance to other MDR/anti-microtubule agents could serve as the basis for the clinical use of EM in combination chemotherapy.

The chemotherapeutic drug, estramustine, has been shown to cause the disassembly of microtubules via binding to microtubule-associated proteins. In this report, estramustine is shown to be a potent inhibitor of mitotic progression in the human prostatic carcinoma cell line, DU 145. Examination of individual living cells via video-enhanced differential interference contrast (DIC) optics shows that the drug delays the onset of anaphase, reduces anaphase spindle-pole elongation (anaphase B), and delays cytokinesis. In addition, immunofluorescent studies demonstrate that estramustine causes a rapid disorganization of the mitotic apparatus at significantly lower concentrations than those reported previously. Electron microscopic studies show that microtubule bundles are present in drug-treated mitotic cells in association with kinetochores and centrioles.

Estramustine offers a mechanistically novel therapy for the treatment of prostatic cancer. The drug is composed of oestradiol coupled to nor-nitrogen mustard. The cytotoxic properties of estramustine act independently of its constituent molecules. In vivo and in vitro studies indicate that the drug binds microtubule associated proteins and inhibits microtubule regulated processes. We have lately shown that micromolar levels of estramustine inhibit selected processes in mitosis, suggesting that certain classes of microtubules and/or MAPs are differentially sensitive to the drug. New clinical trials using estramustine and vinblastine on patients with advanced hormone refractory disease suggest that the combination of two antimicrotubule agents acting by means of different target molecules may be important clinically.